Abstract
Zerumbone is an active component of Zingiber zerumbet (L.) Smith and can perform a diverse range of antitumor activities. However, the underlying molecular mechanisms of zerumbone action have not yet been elucidated. The aim of the present study was to investigate the antitumor effects, and the associated molecular mechanisms, of zerumbone in hepatoma HepG2 cells. Treatment with zerumbone markedly induced apoptosis in hepatoma HepG2 cells and suppressed their invasion and metastasis in a dose-dependent manner. Further investigation revealed that treatment with zerumbone led to the dose-dependent induction of apoptosis and cell cycle arrest at G2/M phase in cancer cells. Zerumbone treatment led to the increased expression of p27, cytochrome c, caspase-3 and-9, and Bcl-2-associated X expression, but the decreased expression of cyclin-dependent kinase 1, cyclin B1, B-cell lymphoma-2, focal adhesion kinase, Ras homolog gene family, member A, Rho-associated protein kinase-1, and matrix metalloproteinase-2 and-9 in HepG2 cells. In addition, the phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2, but not C-Jun N-terminal kinase 1/2, was regulated in a dose-dependent manner in response to zerumbone treatment. The results of the current study indicate that zerumbone could be used as potential anticancer agent in for the treatment of hepatoma in the future.